Guanine nucleotide-binding proteins (G proteins) are believed to alternate between an inactive guanosine diphosphate (GDP) state and an active guanosine triphosphate (GTP) bound state. These two states have been linked to the release of a secondary messenger within a cell. The released secondary messenger can function to regulate downstream cell processes.
Secondary messengers include signaling molecules that are rapidly generated/released. These molecules produce cellular responses by activating effector proteins within the cell. Example cellular signaling systems include the phosphoinositol system, the cyclic adenosine monophosphate (cAMP) system, and the arachidonic acid system.
Changes between the different states of the G proteins can be triggered as a result of proteins called G protein-coupled receptors (GPCRs), G protein-linked receptors (GPLR), seven transmembrane domain receptors (7TM receptors) or heptahelical receptors. This protein family includes a variety of transmembrane receptors. These receptors respond to external stimuli (e.g., light, neurotransmitters, odors or hormones) by activating signal transduction pathways internal to the cell. Specifically, ligands bind and activate the transduction pathways thereby causing the G proteins to alternate states. GPCR-related activity is associated with many diseases, and thus, GPCRs are the target of many pharmaceuticals and treatments.
It is believed that over 30% of all drugs on the market target G-protein coupled receptors (GPCRs) and that many of those drugs relate to the production or inhibition of the secondary messenger cAMP. There is an abundance of pathological processes that directly involve cAMP, including neurophysiological, endocrinological, cardiac, metabolic, and immune diseases. In the study of complex mammalian behaviors, technological limitations have prevented spatiotemporally precise control over intracellular signaling processes. Current chemical-based methods for modulating secondary messenger levels, such as cAMP levels, operate relatively slowly and present problems to study activity on the fast timescales that the body uses in connection with certain tissue, such as in nervous or cardiac tissue. These chemical-methods often lack the speed to probe these fast timescales (e.g., while screening for novel therapeutics).